BIOMARKER CORE PROJECT SUMMARY/ABSTRACT The ability to study Alzheimer?s disease (AD) and related disorders has been revolutionized by the development and application of in vivo biomarkers. Analysis of cerebrospinal fluid (CSF), positron emission tomography (PET), and magnetic resonance imaging (MRI) allow operational measurement of amyloid, tau, and neurodegeneration (A/T/N), the major pathophysiological changes that define AD. Moreover, improved sensitivity and specificity of instrumentation applied to biofluid data, of neuroimaging protocols, and of analytic approaches both enable and necessitate the development, refinement, and discovery of novel biomarkers in any comprehensive AD research program. The Columbia University ADRC Biomarker Core embraces these theme and will derive standard biofluid and MRI biomarkers for all ADRC participants; serve as a central hub for human biofluid, PET, and MRI-based biomarker research conducted within the cognitive aging and dementia community at Columbia University; develop and implement novel biomarkers; and provide training opportunities for investigators interested in incorporating AD-related biomarkers into their research. The Biomarker Core leverages unique data sources, infrastructural, and intellectual strengths already in place and comprises a team of close-collaborating investigators instrumental to the majority of ongoing AD biomarker studies at Columbia University. The Biomarker Core will analyze research grade MRI scans acquired from harmonized clinical scans, from ongoing studies, or de novo for neurodegenerative and cerebrovascular markers. The Core features a newly-acquired single molecule array (Simoa) Benchtop Multiplexed Biomarker Detection Analyzer and Mesoscale Discovery (MSD) platform for analysis of CSF and blood and development of novel biomarkers. These resources will be used to derive existing blood- and CSF-based biomarkers and to develop novel ones. The deep biomarker characterization of all ADRC participants and close interaction with the other Cores will increase understanding of disease etiology and heterogeneity. The Biomarker Core has the following aims: 1) To harmonize, bank, and disseminate fluid and neuroimaging biomarker data derived from participants enrolled by the Clinical Core; 2) To quantitate biofluid biomarkers and MRI markers of neurodegeneration and cerebrovascular disease, according to the A/T/N classification scheme; 3) To develop, optimize, and implement biomarkers of the three thematic biological pathways: immune response, cholesterol metabolism, and endosomal trafficking; 4) To provide intellectual, analytic, and infrastructural support to local investigators interested in incorporating blood-based, CSF, MRI, and PET imaging biomarkers into their Alzheimer?s-related research programs; and 5) To provide training and training opportunities for the next generation of diverse scientists interested in incorporating biomarkers into the study of cognitive aging and dementia.